43 research outputs found
Análisis de factores pronósticos clásicos y emergentes en linfomas no Hodgkin de estirpe B. Utilidad pronóstica del mRNA aislado en exosomas de sangre periférica
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 28-06-2017Los
linfomas
no
Hodgkin
de
estirpe
B
son
neoplasias
malignas
de
origen
linfoide,
el
linfoma
difuso
de
célula
grande
y
el
linfoma
folicular
son
las
variantes
más
frecuentes.
Ambas
entidades
han
visto
modificado
su
evolución
natural
tras
la
introducción
del
rituximab,
anticuerpo
monoclonal
anti
CD
20.
Los
factores
pronósticos
clásicos
en
la
era
prerituximab
se
han
visto
modificados
tras
la
introducción
del
anticuerpo
y
algunos
de
ellos
han
perdido
su
valor.
El
tratamiento
con
inmunoquimioterapia
ha
conseguido
aumentar
la
supervivencia
libre
de
progresión
,
la
supervivencia
global
y
las
tasas
de
respuestas
tanto
en
los
linfomas
difusos
de
célula
grande
como
en
los
linfomas
foliculares.
La
adición
del
anticuerpo
ha
conseguido
disminuir
el
porcentaje
de
recaídas
precoces,
entendidas
como
las
que
ocurren
en
los
dos
primeros
años
y
hemos
podido
demostrar
que
las
recaídas
precoces
son
las
que
confieren
peor
pronóstico
en
ambas
entidades
histológicas.
A
pesar
de
las
mejoras
en
los
tratamientos
siguen
existiendo
un
porcentaje
nada
desdeñable
de
pacientes
que
recaen
en
los
primeros
años
tras
el
diagnóstico,
las
recaídas
en
linfomas
difusos
pueden
variar
según
las
series
entre
un
20
y
un
40%
de
los
casos
,
y
de
estas
solo
una
pequeña
minoría
serán
rescatables
con
los
tratamientos
posteriores.
En
el
caso
de
los
linfomas
foliculares
las
tasas
de
recaídas
han
disminuido
considerablemente
tras
la
introducción
del
rituximab
pero
en
nuestra
serie
hasta
un
30%
de
los
pacientes
tratados
con
inmunoterapia
recaen.
Existe
una
evidente
necesidad
de
búsqueda
de
nuevos
factores
pronóstico
que
nos
seleccionen
a
los
pacientes
de
una
forma
más
adecuada.
Sabemos
que
las
características
biológicas
moleculares
pueden
marcar
diferencias
en
el
comportamiento
tumoral
y
es
por
ello
que
decidimos
ahondar
en
el
estudio
molecular
de
los
linfomas
a
través
de
una
fuente
de
material
genético
fácilmente
accesible
como
son
los
exosomas.
En
el
avance
de
la
ciencia
hemos
detectado
material
genético
tumoral
en
la
sangre
de
nuestro
pacientes
y
los
exosomas
emergen
como
una
fuente
de
material
genético
accesible
y
estable,
haciéndolo
idóneo
para
su
estudio.
Hemos
aislado
en
el
plasma
de
pacientes,
exosomas
que
contienen
mRNA
de
genes
que
en
la
literatura
se
han
relacionado
con
el
pronóstico
de
los
linfomas
(
bcl-‐6,
bcl-‐xl,
c-‐myc,
pten,
AKT
y
NF-‐kB)
pre
y
post
tratamiento
con
inmunoquimioterapia
y
hemos
observado
su
valor
pronóstico
en
nuestra
serie
de
pacientes.
Se
observan
diferencias
en
la
expresión
de
mRNA
en
los
exosomas
de
los
pacientes
tras
el
tratamiento
con
inmunoquimioterapia,
la
presencia
de
mRNA
de
bcl-‐6
y
la
pérdida
de
expresión
de
pTEN
tras
los
tratamientos
parece
asociarse
con
peor
pronóstico
y
la
presencia
de
c-‐myc
pre
tratamiento
se
asocia
con
una
respuesta
parcial
de
la
enfermedad.
Existen
diferencias
en
la
expresión
de
bcl-‐6
y
pten
entre
individuos
sanos
y
pacientes
afectos
de
linfoma.
Es
necesario
continuar
esta
línea
de
investigación
para
una
correcta
caracterización
de
los
linfomas
y
poder
diseñar
estrategias
más
precisas
de
tratamiento
acorde
a
las
características
moleculares
de
los
linfomas
Knowledge and Opinions of Healthcare Professionals about Thirdhand Smoke: A Multi-National, Cross-Sectional Study
There is scarce evidence on the knowledge and opinions about third-hand smoke (THS) of
health care professionals. The main aim of this study was to explore the knowledge and opinions
of health care professionals about THS and, secondarily, to explore the factors that are associated
with this knowledge. Cross-sectional study using a snowball sample of multi-national health care
professionals (n = 233). Data were obtained from an exploratory, online questionnaire. The health
care professionals’ knowledge and opinions on THS were described with absolute frequency and
percentage. Chi-square and Fisher-Freeman-Halton exact tests, and simple logistic regression models,
were used to explore the bivariate association between the knowledge of the concept THS and sex,
continent of birth, educational level, occupation, years of experience, and attitude towards smoking.
Finally, a multivariable logistic regression model incorporating all the above variables was fitted.
A total of 65.2% of the participants were unaware of the term THS before the study began. In the
bivariate analysis, an association was found between prior knowledge of the term THS and continent
of birth (p-value = 0.030) and occupation (p-value = 0.014). In the multivariable logistic regression
model, a significant association was observed between prior knowledge of the concept THS and
sex (p-value = 0.005), continent of birth (p-value = 0.012), and occupation (p-value = 0.001). Almost
two out of three health care professionals who participated in our study did not know what THS was.
Educational activities on this topic should be implemented
mRNA in exosomas as a liquid biopsy in non-Hodgkin Lymphoma: a multicentric study by the Spanish Lymphoma Oncology Group
Purpose: To determine the feasibility of mRNAs (C-MYC, BCL-XL, BCL-6, NF-κβ,
PTEN and AKT) in exosomes of plasma as a liquid biopsy method for monitoring and
prognostic evolution in B-cell lymphomas.
Patients and Methods: Exosomes were isolated from 98 patients with B-cell
Lymphoma and 68 healthy controls. mRNAs were analyzed by quantitative PCR. An
additional 31 post-treatment samples were also studied.
Results: In the general and follicular lymphoma series, the presence of AKT
mRNA was associated with poor response to rituximab-based treatment. Patients
with first relapse or disease progression showed a lower percentage of PTEN and
BCL-XL mRNA. The presence of BCL-6 mRNA was associated with a high death rate.
The absence of PTEN mRNA in the general series, and presence of C-MYC mRNA in
follicular lymphomas, were associated with short progression-free survival. BCL-6 and
C-MYC mRNA were independent prognostic variables of overall survival. C-MYC mRNA
may provide prognostic information with respect to overall survival. BCL-XL mRNA
and increase of BCL-6 mRNA in post-treatment samples could serve as molecular
monitoring markers.
Conclusions: This is the first large study to evaluate the prognostic and predictive
values of pretreatment tumor-associated mRNA in exosomes. BCL-6 and C-MYC mRNA
positivity in pretreatment samples were predictors of worse PFS compared to patients
with mRNA negativity. C-MYC mRNA positivity was also a statistically significant
predictor of inability to obtain complete response with first-line therapyThis study was supported by grants FIS-PI08/0862, and SAF2010-20750. During this study, V. García received Fundación AECC and RTICC-RD2012/0036/0006 fellowship
Chronodisruption and Ambulatory Circadian Monitoring in Cancer Patients: Beyond the Body Clock
Purpose of Review: Circadian rhythms impose daily rhythms a remarkable variety of metabolic and physiological functions, such as cell proliferation, inflammation, and DNA damage response. Accumulating epidemiological and genetic evidence indicates that circadian rhythms’ disruption may be linked to cancer. The integration of circadian biology into cancer research may offer new options for increasing cancer treatment effectiveness and would encompass the prevention, diagnosis, and treatment of this disease. Recent Findings: In recent years, there has been a significant development and use of multi-modal sensors to monitor physical activity, sleep, and circadian rhythms, allowing, for the very first time, scaling accurate sleep monitoring to epidemiological research linking sleep patterns to disease, and wellness applications providing new potential applications. Summary: This review highlights the role of circadian clock in tumorigenesis, cancer hallmarks and introduces the state-of-the-art in sleep-monitoring technologies, discussing the eventual application of insights in clinical settings and cancer research.publishersversionpublishe
Chronodisruption and Ambulatory Circadian Monitoring in Cancer Patients: Beyond the Body Clock.
Purpose of Review Circadian rhythms impose daily rhythms a remarkable variety of metabolic and physiological functions,
such as cell proliferation, infammation, and DNA damage response. Accumulating epidemiological and genetic evidence
indicates that circadian rhythms’ disruption may be linked to cancer. The integration of circadian biology into cancer research
may ofer new options for increasing cancer treatment efectiveness and would encompass the prevention, diagnosis, and
treatment of this disease.
Recent Findings In recent years, there has been a signifcant development and use of multi-modal sensors to monitor physical
activity, sleep, and circadian rhythms, allowing, for the very frst time, scaling accurate sleep monitoring to epidemiological
research linking sleep patterns to disease, and wellness applications providing new potential applications.
Summary This review highlights the role of circadian clock in tumorigenesis, cancer hallmarks and introduces the stateof-the-art in sleep-monitoring technologies, discussing the eventual application of insights in clinical settings and cancer
research.post-print1077 K
Chronodisruption and Ambulatory Circadian Monitoring in Cancer Patients: Beyond the Body Clock
Purpose of Review: Circadian rhythms impose daily rhythms a remarkable variety of metabolic and physiological functions, such as cell proliferation, inflammation, and DNA damage response. Accumulating epidemiological and genetic evidence indicates that circadian rhythms’ disruption may be linked to cancer. The integration of circadian biology into cancer research may offer new options for increasing cancer treatment effectiveness and would encompass the prevention, diagnosis, and treatment of this disease. Recent Findings: In recent years, there has been a significant development and use of multi-modal sensors to monitor physical activity, sleep, and circadian rhythms, allowing, for the very first time, scaling accurate sleep monitoring to epidemiological research linking sleep patterns to disease, and wellness applications providing new potential applications. Summary: This review highlights the role of circadian clock in tumorigenesis, cancer hallmarks and introduces the state-of-the-art in sleep-monitoring technologies, discussing the eventual application of insights in clinical settings and cancer researchThis work was supported in part by CLARIFY project, within European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 875160, Instituto de Fomento de la Región de Murcia (INFO) and the European Regional Development Fund (FEDER
Assessing the risk of cardiovascular events in patients receiving immune checkpoint inhibitors
Funding Information: This article is part of the CLARIFY project, supported by the European Union Horizon 2020 Research and Innovation Program under grant agreement number 875160. Publisher Copyright: Copyright © 2022 Torrente, Blanco, Franco, Garitaonaindia, Calvo, Collazo-Lorduy, Gutiérrez, Sánchez, González-del-Alba, Hernández, Méndez, Cantos, Núñez, Sousa and Provencio.Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, despite their excellent therapeutic effect, these medications typically result in a broad spectrum of toxicity reactions. Immune-related cardiotoxicity is uncommon but can be potentially fatal, and its true incidence is underestimated in clinical trials. The aim of this study is to assess the incidence and identify risk factors for developing a cardiac event in patients treated with ICIs. Methods: We conducted a single-institution retrospective study, including patients treated with ICIs in our center. The main outcomes were cardiac events (CE) and cardiovascular death. Results: A total of 378 patients were analyzed. The incidence of CE was 16.7%, during a median follow-up of 50.5 months. The multivariable analysis showed that age, a history of arrhythmia or ischemic heart disease, and prior immune-related adverse events were significantly associated with CE. Conclusion: CE during ICI treatment are more common than currently appreciated. A complete initial cardiovascular evaluation is recommended, especially in high-risk patients, being necessary a multidisciplinary approach of a specialized cardio-oncology team.publishersversionpublishe
Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2– advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial
Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone.Methods: CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1.Results: A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade >= 3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade >= 3 neutropenia and anemia. Efficacy results were consistent with the global study.Conclusions: Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2-ABC, including populations of interest (NCT02941926).Trial registration: ClinicalTrials.gov NCT0294192